ADHD is associated with deficits in cognitive functions. These include such executive functions as reaction time, motor and interference inhibition, sustained attention, and working memory.
To what extent can ADHD medications compensate for such deficits? A recent meta-analysis by a European study team has explored this question. It suggests that while medication cannot completely reverse deficits in executive functions, it can lead to significant improvements.
Based on consistent evidence from many randomized double-blind controlled trials (RCTs) measuring behavioral improvements, first line treatment for ADHD is with stimulant medication while second-line treatment (for stimulant non-responders, or poor tolerability) is with non-stimulant medication (atomoxetine, viloxazine, guanfacine and clonidine).
This systematic literature search yielded eighteen RCTs, not all of which covered the same executive functions or medicines.
Meta-analyses yielded the following results:
Reaction Time
Eleven RCTs, encompassing 925 participants, found a small-to-medium effect size improvement with methylphenidate. Variation (heterogeneity) among these studies was moderate, and there was no sign of publication bias.
Four RCTs with a total of 286 participants similarly reported a small-to-medium effect size improvement with atomoxetine. Again, heterogeneity was moderate, with no indication of publication bias.
Attention
Sixteen RCTs, with a combined 1,335 participants, found a medium effect size improvement with methylphenidate. Heterogeneity was moderate, and there was some indication of publication bias. No effort was made to correct for publication bias.
Three RCTs, encompassing 254 persons, found a medium effect size improvement with atomoxetine. Heterogeneity was moderate, with no evidence of publication bias.
Inhibition
Thirteen RCTs, with a total of 1,201 participants, found a small-to-medium effect size improvement with methylphenidate. Heterogeneity was moderate, with marginal indication of publication bias.
Six RCTs with a combined 753 individuals, reported a medium effect size improvement with atomoxetine. Heterogeneity was high, but there was no evidence of publication bias.
Working Memory
Nine RCTs, with a total of 1,025 participants, found a small-to-medium effect size improvement with methylphenidate. Heterogeneity was moderate, with no indication of publication bias.
Three RCTs with a combined 132 individuals, reported a statistically nonsignificant small-to-medium effect size improvement with atomoxetine. Heterogeneity was moderate, with no indication of publication bias. The nonsignificant outcome may have been due to the much smaller number of participants.
The team concluded, “these meta-analyses of chronic effects of stimulants and non-stimulants on executive functions in ADHD showed significant improvements with both methylphenidate and with atomoxetine in all cognitive domains tested with relatively similar effect sizes, and no statistical differences between them. The findings hence suggest comparable positive effects of both ADHD medication types on the most relevant executive functions in ADHD, suggesting for the first time that stimulant and non-stimulant ADHD medications, when taking [sic] longer-term, not only improve behavioural symptoms of ADHD, but also improve executive function performance, and to a similar degree.”
Ferdous Isfandnia, Sahid El Masri, Joaquim Radua, and Katya Rubia, “The Effects of Chronic Administration of Stimulant and Non-stimulant Medications on Executive Functions in ADHD: A Systematic Review and Meta-Analysis,” Neuroscience and Biobehavioral Reviews (2024), https://doi.org/10.1016/j.neubiorev.2024.105703.
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